The purpose of this research program is to improve our current understanding of the regulation of the pulmonary circulation and peripheral vascular bed by nervous, endocrine and ionic factors. The actions of prostaglandins, prostacyclins, thromboxanes, amine and peptide hormones will be investigated in the pulmonary and peripheral circulations. A variety of techniques will be used to investigate the actions of vasoactive substances in the pulmonary and systemic circulations in a number of laboratory species. Right heart and transseptal catheterizaiton techniques will be used to maintain pulmonary blood flow constant in the intact chest animal. Hindlimb, renal and mesenteric blood flows will be measured with electromagnetic flowmeters and in some experiments maintained constant with a pump. Factors which influence synthesis and metabolism of prostaglandins, prostacyclins and thromboxanes in the lung, intestine and kidney will be investigated. In these experiments, the influence of embolization, hypoxia, acidosis, endotoxin and hypercapnia on responses to vasoactive hormones will be investigated in the pulmonary and systemic circulations. Studies in progress show that prostaglandins and prostacyclins have marked activity on the canine and feline pulmonary vascular beds and on several peripheral vascular beds in these species. Prostacyclin (PGI2) has significant vasodilator activity in the pulmonary vascular bed and to date is the only known product of the arachidonic acid cascade which dilates both he pulmonary and systemic vascular beds. PGI2 also has marked antiplatelet aggregating activity in the pulmonary vascular bed. Results of these experiments suggest that prostacyclin-like substances may be useful in the treatment of pulmonary hypertensive and thromboembolic diseases.